Study of the regulation of the endocannabinoid system in a virus model of multiple sclerosis reveals a therapeutic effect of palmitoylethanolamide

• Published in: The European journal of neuroscience Vol. 28; no. 4; pp. 633 - 641
• Main Authors: Loría, Frida, Petrosino, Stefania, Mestre, Leyre, Spagnolo, Alessandra, Correa, Fernando, Hernangómez, Miriam, Guaza, Carmen, Di Marzo, Vincenzo, Docagne, Fabian
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-2008
• Subjects: Animals; Anti-Inflammatory Agents - therapeutic use; Antiviral Agents - therapeutic use; Cannabinoid Receptor Modulators - metabolism; Cannabinoid Receptor Modulators - therapeutic use; cannabinoids; Cytokines - genetics; Cytokines - immunology; Disease Models, Animal; Endocannabinoids; Ethanolamines; Female; Humans; Mice; Motor Activity - physiology; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Multiple Sclerosis - physiopathology; Multiple Sclerosis - virology; Mus musculus; neuroinflammation; Pain - drug therapy; Palmitic Acids - metabolism; Palmitic Acids - therapeutic use; PPAR alpha - genetics; PPAR alpha - metabolism; Receptor, Cannabinoid, CB1 - genetics; Receptor, Cannabinoid, CB1 - metabolism; Receptor, Cannabinoid, CB2 - genetics; Receptor, Cannabinoid, CB2 - metabolism; Rotarod Performance Test; Signal Transduction - physiology; TaqMan RT-PCR; Theiler's virus; Theilovirus - immunology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2008.06377.x

Cannabinoids have recently been approved as a treatment for pain in multiple sclerosis (MS). Increasing evidence from animal studies suggests that this class of compounds could also prove efficient to fight neurodegeneration, demyelination, inflammation and autoimmune processes occurring in this pathology. However, the use of cannabinoids is limited by their psychoactive effects. In this context, potentiation of the endogenous cannabinoid signalling could represent a substitute to the use of exogenously administrated cannabinoid ligands. Here, we studied the expression of different elements of the endocannabinoid system in a chronic model of MS in mice. We first studied the expression of the two cannabinoid receptors, CB1 and CB2, as well as the putative intracellular cannabinoid receptor peroxisome proliferator‐activated receptor‐α. We observed an upregulation of CB2, correlated to the production of proinflammatory cytokines, at 60 days after the onset of the MS model. At this time, the levels of the endocannabinoid, 2‐arachidonoylglycerol, and of the anti‐inflammatory anandamide congener, palmithoylethanolamide, were enhanced, without changes in the levels of anandamide. These changes were not due to differences in the expression of the degradation enzymes, fatty acid amide hydrolase and monoacylglycerol lipase, or of biosynthetic enzymes, diacylglycerol lipase‐α and N‐acylphosphatidylethanolamine phospholipase‐D at this time (60 days). Finally, the exogenous administration of palmitoylethanolamide resulted in a reduction of motor disability in the animals subjected to this model of MS, accompanied by an anti‐inflammatory effect. This study overall highlights the potential therapeutic effects of endocannabinoids in MS.